A Research Study Looking Into How Ziltivekimab Works Compared to Placebo in Participants With Heart Failure and Inflammation

Primary Outcome Measures

1. Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score (KCCQ-CSS)
   Measured as score (score on scale; range; 0-100). The KCCQ is a disease-specific health status instrument composed of 23 items that quantify the domains of physical limitation, symptoms, self-efficacy, social limitation, and health-related quality of life limitation from heart failure. The overall summary score and all domains have been independently demonstrated to be valid, reliable, and responsive to clinical change. CSS scores range from 0 to 100 and lower scores represent more severe symptoms and/or limitations and scores of 100 indicate no symptoms, no limitations, and excellent quality of life.

Secondary Outcome Measures

1. Participant achieving threshold for clinically meaningful within-participant change in KCCQ CSS (yes/no)
   Measured as count of participants. The KCCQ is a disease-specific health status instrument composed of 23 items that quantify the domains of physical limitation, symptoms, self-efficacy, social limitation, and health-related quality of life limitation from heart failure. The overall summary score and all domains have been independently demonstrated to be valid, reliable, and responsive to clinical change. CSS scores range from 0 to 100 and lower scores represent more severe symptoms and/or limitations and scores of 100 indicate no symptoms, no limitations, and excellent quality of life.
2. Participant achieving threshold for clinically meaningful within-participant change in 6-minute walk distance (6MWD) (yes/no)
   Measured as count of participants.
3. Participants improving 5 points or more in KCCQ-CSS (yes/no)
   Measured as count of participants. The KCCQ is a disease-specific health status instrument composed of 23 items that quantify the domains of physical limitation, symptoms, self-efficacy, social limitation, and health-related quality of life limitation from heart failure. The overall summary score and all domains have been independently demonstrated to be valid, reliable, and responsive to clinical change. CSS scores range from 0 to 100 and lower scores represent more severe symptoms and/or limitations and scores of 100 indicate no symptoms, no limitations, and excellent quality of life.
4. Participants improving 10 points or more in KCCQ-CSS (yes/no)
   Measured as count of participants. The KCCQ is a disease-specific health status instrument composed of 23 items that quantify the domains of physical limitation, symptoms, self-efficacy, social limitation, and health-related quality of life limitation from heart failure. The overall summary score and all domains have been independently demonstrated to be valid, reliable, and responsive to clinical change. CSS scores range from 0 to 100 and lower scores represent more severe symptoms and/or limitations and scores of 100 indicate no symptoms, no limitations, and excellent quality of life.
5. Change in subscales of KCCQ (total symptom score, physical limitations score, social limitations score, and health-related quality of life)
   Measured as score (score on scale; range 0-100). The KCCQ is a disease-specific health status instrument composed of 23 items that quantify the domains of physical limitation, symptoms, self-efficacy, social limitation, and health-related quality of life limitation from heart failure. The overall summary score and all domains have been independently demonstrated to be valid, reliable, and responsive to clinical change. CSS scores range from 0 to 100 and lower scores represent more severe symptoms and/or limitations and scores of 100 indicate no symptoms, no limitations, and excellent quality of life.
6. Change in six-minute walk distance (6MWD)
   Measured in meters.
7. Change in high-sensitivity C-reactive protein (hs-CRP)
   Measured as ratio to baseline.
8. Participants experiencing improvement in New York heart association (NYHA) Class (yes/no)
   Measured as count of participants. The New York Heart Association (NYHA) classification provides a simple way of classifying the extent of heart failure (HF). It classifies patients in one of four categories based on their limitations during physical activity - Class I: Participant with cardiac disease but without resulting limitations of physical activity, Class II: Participants with cardiac disease resulting in slight limitation of physical activity, Class III: Participants with cardiac disease resulting in marked limitation of physical activity, Class IV: Participants with cardiac disease resulting in inability to carry on any physical activity without discomfort.
9. Change in N-terminal-pro-brain natriuretic peptide (NT-proBNP)
   Measured as ratio to baseline.
10. Change in eGFR (CKD-EPI)
    eGFR (CKD-EPI) is estimated glomerular filtration rate chronic kidney disease - epidemiology collaboration. Measured in milliliter per minute per 1.73 square meter (ml/min/1.73\^2).